7. PROJECT SUMMARY/ABSTRACT This resubmitted High-End Instrumentation proposal requests funds for the purchase of a US-manufactured NovaSeqTM 6000 Sequencing System with installation, training and a 12-month warranty from Illumina, Inc, San Diego, CA. Institutional support has been committed to cover personnel salaries, consumables, and the service contract for the operational lifetime of the instrument. The system will be housed with our other existing Illumina sequencing platforms in the National Cancer Institute (NCI)-designated Sidney Kimmel Cancer Center (SKCC) fee-for-service MetaOmics Shared Resource core facility at Thomas Jefferson University (TJU) in central Philadelphia. The NovaSeq 6000 will provide the necessary capacity for current demands at TJU, including the SKCC and its regional consortium partner Drexel University. Founded in 2006, the MetaOmics Shared Resource facility has been instrumental in promoting genomics research by facilitating hundreds of research projects utilizing a wide variety of experimental systems. The MetaOmics Shared Resource facility initially offered high- throughput sequencing using two Life Technologies/Applied Biosystems 5500xl Genetic Analyzers and two Ion Torrent PGM instruments, which became outmoded and were replaced by Illumina systems. The availability of these platforms has spurred an exponential increase in sequencing demand that has rapidly exceeded the capacity of our current MetaOmics Shared Resource core instrumentation. Acquisition of the NovaSeq 6000 System will ensure that the laboratories supported by the MetaOmics Shared Resource facility, especially the NIH-funded investigators described herein, as well as young investigators who rely on MetaOmics Shared Resource core facility resources for their first NIH grant proposals, will continue to have access to instrumentation and genomics/bioinformatics support needed to utilize next generation sequencing (NGS) technology. The NovaSeq 6000 Sequencing System offers higher capacity, faster turnaround and more cost-effective sequencing, with improved scalability to achieve up to 6000 gigabases (Gb) output per run and extensive multi- omics applications so that up to 48 whole human genomes can be efficiently characterized in a single cost- effective sequencing run. Characterization of these genomic features will lead to a better understanding of Mendelian diseases, complex traits and mechanisms of tumorigenesis, metastasis and therapeutic response. The technical capabilities of the NovaSeq 6000 Sequencing System greatly exceed those of the outmoded NGS instruments currently available at TJU or elsewhere in the Philadelphia region. The strengths of this proposal include the support from the NCI-designated SKCC, the experience in biotechnology and bioinformatics of the PI and other key personnel in overseeing the MetaOmics Shared Resource, the large-scale infrastructure of TJU including the nearby Computational Medicine Center, a productive investigator user base, and our commitment to ensure that acquisition of this high-end instrumentation will have a positive and long-lasting impact on biomedical research at TJU and beyond.